Levels of pro-opiomelanocortin and prolactin mRNA in the fetal sheep pituitary following hypoxaemia and glucocorticoid treatment in late gestation

Matthews, Stephen G.; Challis, John

doi:10.1677/joe.0.1470139

Cited by 34 publications

(13 citation statements)

References 23 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypoxemia-induced increases in fetal plasma concentrations of ACTH and cortisol, appropriate for the degree of hypoxemia and the gestational age of the fetus (10,30 -33), were prevented by maternal dexamethasone, consistent with previous studies in fetal sheep (10,34,35). Both direct fetal i.v.…”

Section: Dexamethasone and The Materno-fetal Hpa Axissupporting

confidence: 88%

Pituitary-Adrenal Responses to Acute Hypoxemia During and After Maternal Dexamethasone Treatment in Sheep

et al. 2004

View full text Add to dashboard Cite

The effects of maternal dexamethasone treatment on hypothalamic-pituitary-adrenal axis function were determined during basal and hypoxemic conditions in maternal and fetal sheep. Under halothane, ewes and their fetuses were catheterized at 117 d gestation (term ϭ 145 d). Starting at 124 d, the ewes received i.m. injections of two doses of either dexamethasone (12 mg) or saline at 24-h intervals. All animals experienced one episode of hypoxemia when the dexamethasone was present in the maternal and fetal circulations [125 Ϯ 1 d (H1)] and a second episode of hypoxemia when the steroid was no longer detectable in either the maternal or fetal circulations [128 Ϯ 1 d (H2)]. The fall in partial pressure of oxygen in arterial blood in response to hypoxia was similar in the two episodes in both the fetal and the maternal blood. Maternal dexamethasone treatment diminished maternal and fetal basal plasma cortisol but not ACTH during the normoxic period of H1 but not H2. In control animals, hypoxemia induced increases in fetal but not maternal ACTH and cortisol concentrations. In dexamethasone-treated animals, maternal ACTH and cortisol concentrations also remained unchanged from baseline in both H1 and H2. In contrast, fetal plasma ACTH and cortisol responses to hypoxemia were significantly suppressed during H1 but not H2. Correlation of fetal plasma ACTH and cortisol concentrations suggested diminished cortisol output without a change in adrenocortical responsiveness in dexamethasone-treated fetuses during H1 but not H2. Since the pioneering discovery of Liggins (1) that glucocorticoids are essential for the maturation of fetal systems in preparation for extrauterine life, synthetic glucocorticoids, such as dexamethasone, have been used routinely in human clinical practice to treat pregnant women who are at risk of preterm delivery (2-4). Such prophylactic treatment mimics the normal prepartum increase in endogenous cortisol output by the fetal adrenal that switches tissue accretion to differentiation (5). Antenatal glucocorticoid treatment has resulted in significant decreases in the incidence of respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, and neonatal mortality associated with preterm birth (3,6).Despite the clear benefits of antenatal glucocorticoid therapy, concerns have been expressed about the safety of the current dosing regimen, in particular with regards to maternal and fetal adrenal suppression resulting from negative feedback by the synthetic steroid (4). In addition, the effects of synthetic glucocorticoids on the fetal defense responses to hypoxemic insults have been identified by the National Institutes of Health in the United States as an area of research needed to guide intrapartum clinical care (4). This is important for two reasons. First, the ovine hypothalamic-pituitary-adrenal (HPA) axis is activated in response to acute hypoxemia in the mother and the fetus and plays an integral role in the fetal defense response to acute hypoxemia (7). Second, episodes of ...

show abstract

Section: Dexamethasone and The Materno-fetal Hpa Axissupporting

confidence: 88%

Pituitary-Adrenal Responses to Acute Hypoxemia During and After Maternal Dexamethasone Treatment in Sheep

et al. 2004

View full text Add to dashboard Cite

show abstract

“…It appears that the decrease in 11␤HSD-2 mRNA levels in response to cortisol is not through an indirect action of cortisol at the fetal pituitary, as there was no change in circulating ACTH in response to the intrafetal cortisol infusion. It has been reported that intrafetal infusion of cortisol before the prepartum activation of the fetal pituitaryadrenal axis inhibits fetal ACTH responses to stimulation by corticotrophin releasing factor [17] or acute stressors such as hypoxemia [18], but does not suppress basal ACTH secretion or steady-state expression of the ACTH precursor, proopiomelanocortin (POMC), in the fetal pituitary [19]. In contrast, cortisol infusion after 140 days gestation suppresses basal and stimulated ACTH concentrations [17,20].…”

Section: Discussionmentioning

confidence: 99%

A Premature Increase in Circulating Cortisol Suppresses Expression of 11β Hydroxysteroid Dehydrogenase Type 2 Messenger Ribonucleic Acid in the Adrenal of the Fetal Sheep1

Ross

McMillen

Adams

et al. 2000

Biology of Reproduction

View full text Add to dashboard Cite

We have investigated the effect of intrafetal cortisol administration, before the normal prepartum cortisol surge, on the expression of 11beta hydroxysteroid dehydrogenase (11betaHSD) type 2 mRNA in the fetal adrenal. We also determined whether increased fetal cortisol concentrations can stimulate growth of the fetal adrenal gland or increase expression of adrenal steroidogenic enzymes. Cortisol (hydrocortisone succinate: 2.0-3.0 mg in 4.4 ml/24 h) was infused into fetal sheep between 109 and 116 days of gestation (cortisol infused; n = 12), and saline was administered to control fetuses (saline infused; n = 13) at the same age. There was no effect of cortisol infusion on the fetal adrenal:body weight ratio (cortisol: 101.7 +/- 5.3 mg/kg; saline: 108.2 +/- 4.3 mg/kg). The ratio of adrenal 11betaHSD-2 mRNA to 18S rRNA expression was significantly lower, however, in the cortisol-infused group (0.75 +/- 0.02) compared with the group receiving saline (1.65 +/- 0.14). There was no significant effect of intrafetal cortisol on the relative abundance of adrenal CYP11A1, CYP17, CYP21A1, and 3betaHSD mRNA. A premature elevation in fetal cortisol therefore resulted in a suppression of adrenal 11betaHSD-2. Increased intra-adrenal exposure to cortisol at this stage of gestation is, however, not sufficient to promote adrenal growth or steroidogenic enzyme gene expression.

show abstract

“…Brains were removed, weighed, and rapidly frozen on dry ice and stored at −80 °C until molecular analysis. The method for in situ hybridisation has been described in detail previously (26). Coronal cyrosections (12 µm) were mounted onto (poly)‐L‐lysine (Sigma Chemical, St Louis, MO, USA)‐coated slides, dried, and postfixed with 4% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

Chronic Prenatal Ethanol Exposure Alters Glucocorticoid Signalling in the Hippocampus of the Postnatal Guinea Pig

Iqbal¹,

Brien

Banjanin³

et al. 2005

J Neuroendocrinology

View full text Add to dashboard Cite

The present study tested the hypothesis that chronic prenatal ethanol exposure causes long-lasting changes in glucocorticoid signalling in postnatal offspring. Pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight/day), isocaloric-sucrose/pair-feeding or water throughout gestation, and maternal saliva cortisol concentration was determined 2 h after treatment at different stages of gestation. Electrically-stimulated release of glutamate and GABA, in the presence or absence of dexamethasone, as well as glucocorticoid and mineralocorticoid receptor mRNA expression, was determined in the hippocampus and prefrontal cortex of adult offspring of treated pregnant guinea pigs. Maternal saliva cortisol concentration increased throughout pregnancy, which was associated with increased foetal plasma and amniotic fluid cortisol concentration. Ethanol administration to pregnant guinea pigs increased maternal saliva cortisol concentration during early and mid-gestation. In late gestation, ethanol administration did not increase saliva cortisol concentration above that induced by pregnancy. Chronic prenatal ethanol exposure had no effect on stimulated glutamate or GABA release, but selectively prevented dexamethasone-mediated suppression of stimulated glutamate release, and decreased expression of mineralocorticoid, but not glucocorticoid, receptor mRNA in the hippocampus of adult offspring. These data indicate that maternal ethanol administration leads to excessively increased maternal cortisol concentration that can impact negatively the developing foetal brain, leading to persistent postnatal deficits in glucocorticoid regulation of glutamate signalling in the adult hippocampus.

show abstract

Levels of pro-opiomelanocortin and prolactin mRNA in the fetal sheep pituitary following hypoxaemia and glucocorticoid treatment in late gestation

Cited by 34 publications

References 23 publications

Pituitary-Adrenal Responses to Acute Hypoxemia During and After Maternal Dexamethasone Treatment in Sheep

Pituitary-Adrenal Responses to Acute Hypoxemia During and After Maternal Dexamethasone Treatment in Sheep

A Premature Increase in Circulating Cortisol Suppresses Expression of 11β Hydroxysteroid Dehydrogenase Type 2 Messenger Ribonucleic Acid in the Adrenal of the Fetal Sheep1

Chronic Prenatal Ethanol Exposure Alters Glucocorticoid Signalling in the Hippocampus of the Postnatal Guinea Pig

Contact Info

Product

Resources

About